Causes and Genetics of ARPKD
Autosomal Recessive Polycystic Kidney Disease (ARPKD) is caused by mutations in a single gene known as PKHD1. This gene provides instructions for producing a protein called fibrocystin (or polyductin), which is important for the normal development of kidney tubules and bile ducts in the liver. Let’s learn more about the causes and genetics of ARPKD below.
Unlike autosomal dominant conditions, ARPKD follows a recessive inheritance pattern. This means that:
- Both parents must carry one copy of the faulty PKHD1 gene.
- A child has a 25% chance of inheriting the condition if both parents are carriers.
- There’s a 50% chance the child will be a carrier but not affected.
- There’s a 25% chance the child will inherit neither faulty gene.
In most cases, carrier parents are completely healthy and unaware they have a mutated gene. Many only discover their carrier status after having an affected child. For families with a known history of ARPKD, doctors strongly recommend genetic counselling.
In South Africa, specialised centres and academic hospitals offer genetic testing, but access is limited in some areas due to costs and the availability of laboratory resources. Many families rely on clinical observation and imaging rather than DNA confirmation.
Causes and Genetics of ARPKD
The severity of ARPKD doesn’t always correlate with the specific genetic mutation. Two siblings with the same faulty gene may have very different outcomes — one may survive into adulthood, while another may experience complications early in life.
It’s important to note that ARPKD is not caused by anything the parents did during pregnancy. It is not related to lifestyle, diet, or environmental exposures. This can be a great comfort to families dealing with feelings of guilt or confusion after diagnosis.
Understanding the genetic foundation of ARPKD allows families to make informed decisions about future pregnancies, often with the help of prenatal testing or pre-implantation genetic diagnosis (PGD) if they pursue fertility treatment.
Genetics and Family Planning
Understanding the recessive inheritance pattern of ARPKD is key to helping families navigate future pregnancies and make informed choices. Genetic counselling offers valuable insight into the risks of recurrence, especially for parents who have already had one affected child. Where available, prenatal testing and pre-implantation genetic diagnosis (PGD) can provide options for early detection or prevention — tools that empower families to prepare with confidence and clarity.
Beyond the Genetics: Supporting Families
While the condition is genetic, it’s important to reassure families that ARPKD is not the result of anything they did wrong. Guilt is common after a diagnosis, but recognising that the cause lies in unseen genetic mutations can bring some emotional relief. In South Africa, improved access to genetic services and education can help demystify the condition and support early diagnosis — especially in families who may not realise they carry the gene.
